Biomedical research has made rapid progress based on sequential processing of biological samples. Sequential processing techniques have resulted in important discoveries in a variety of biologically related fields, including, among others, genetics, biochemistry, immunology and enzymology. Historically, sequential processing involved the study of one or two biologically relevant molecules at the same time. These original sequential processing methods, however, were quite slow and tedious. Study of the required number of samples (up to tens of thousands) was time consuming and costly.
A breakthrough in the sequential processing of biological specimens occurred with the development of techniques of parallel processing of the biological specimens, using fluorescent marking. A plurality of samples are arranged in arrays, referred to herein as microarrays, of rows and columns into a field, on a substrate slide or similar member. The specimens on the slide are then biochemically processed in parallel. The specimen molecules are fluorescently marked as a result of interaction between the specimen molecule and other biological material. Such techniques enable the processing of a large number of specimens very quickly.
A significant challenge exists in the scanning of such microarrays, due to their very high content, the relatively large size of the field, and the requirement of very high optical resolution of the scanning system due to the small size of the specimens. An improved system and method for scanning a plurality of specimens arranged within a scan area on a substrate, such as a slide, was presented in co-owned U.S. patent application Ser. No. 09/289,799 filed Apr. 9, 1999. In that application, a system was disclosed wherein successive portions of an array of small biological specimens are imaged using a CCD camera. The x,y coordinates of each successive portion within the array are also determined. The array is moved by a precision staging system to accurately locate each successive portion in the array. The separate data portions are then arranged together using the coordinates of each portion to produce a complete data image of the array, without any geometric adjustment or matching necessary between successive portions.
These scanning systems require high precision in the location of the staging area relative to the camera. When errors are introduced between the staging area and the camera, the precise location of each data portion may vary slightly, thereby making the arrangement of the image portions more difficult. What is needed is a system that detects any systematic alignment errors and compensates for these errors prior to assembling the complete image.